a. Field of the Invention
The present invention relates generally to the methods for the treatment of Alzheimer's Disease (AD) and Autism Spectrum Disorder (ASD) and more particularly to methods for treatment of AD and ASD by administration of an alkyl ester of imidazole carboxylic acid in order to maintain the intracellular/extracellular osmolyte gradient in the central nervous system (CNS).
b. Background
Alzheimer's Disease (AD) is a neurodegenerative disease that slowly destroys memory and thinking skills, and eventually impairs the ability to carry out simple activities of daily living. The first symptoms of AD which are memory loss, language problems, and unpredictable behavior generally appear after age 60. It is estimated that 2.4 to 4.5 million Americans are living with AD (www.nia.nih.gov/Alzheimers/Publications/adfact.htm)
The root cause of AD is unknown but genetic and environmental factors are suspected. The disease progresses over time, presenting in the early stage with short-term memory and cognitive difficulties e.g. repeating questions, poor judgment, and mood and personality changes. The disease then progresses to moderate AD in which parts of the brain are affected that control language, reasoning, sensory processing and conscious thought. Often by this stage of AD, people withdraw from social interaction. In the final stage of AD, people are unable to communicate and they become completely dependent on others for their care.
The progression of AD is positively correlated with the development of neurofibrillary tangles and amyloid plaques that spread throughout the brain and inversely correlated with loss of neurons.
Four medications are currently approved by the U.S. Food and Drug Administration to treat AD: Donepezil (Aricept®), rivastigmine (Exelon®), galantamine (Razadyne®), and memantine (Namenda®). These drugs work by regulating neurotransmitters and may help to maintain thinking, memory, and language skills for a few months to years, however, they do not change the underlying disease process.
Autism Spectrum Disorder (ASD) has many similar symptoms as Alzheimer's Disease (AD). Like AD, the severity of symptoms of ASD are on a spectrum. Autism Spectrum Disorder, also known as Pervasive Developmental Disorders (PDD), is generally considered to encompass five more particular disorders: Autism; Asperger Syndrome; Rett Syndrome; Childhood Disintegrative Disorder; and Pervasive Developmental Disorder Not Otherwise Specified (atypical autism). Childhood autism, also known as autistic disorder or infantile autism, is a neuro-developmental condition that is characterized by impairment in social interaction, impairment in communication and restricted or stereotyped patterns of behavior and interest usually manifested before the age of 3 years. Common symptoms of ASD include: impaired social and communication skills (verbal and nonverbal); delayed or unusual speech patterns; hyper or hypo sensitivity to light, sound, crowd and other external stimulation; some degree of fine and gross motor difficulty; repetitive behaviors and ritualized activities; aloofness or disengagement with surrounding environment, inability to handle stress or change in routine or environment; some patients have a degree of mental retardation and one in four develop seizures. The severity of these symptoms is very individualized in persons diagnosed with ASD.
The incidence of ASD has increased dramatically over the last decade, and today 1 in 100 children are diagnosed as having ASD. The root cause of ASD still eludes the medical community, but several factors have been implicated such as hereditary, heavy metal toxicity, vaccinations, exposure to high amounts of Pitocin (oxytocin) and/or opioids during birth, food allergies, and vitamin and mineral deficiencies.
Currently only one medication, risperidone, has been approved by the FDA for the symptomatic treatment of irritability in autistic children. Several medications have been used “off-label” to help lessen some of the symptoms associated with ASD, but with limited effectiveness. Some of these medications are antipsychotic medications, antidepressants such as Selective Serotonin Reuptake Inhibitors (SSRIs), alpha adrenergic agonists, anticonvulsants, and stimulants such as Ritalin or Provigil. (http://autism.about.com/od/treatmentoptions/p/drugtreatments.htm).
Accordingly, there exists a need for a method for treatment of AD and ASD that approaches the fundamental cause of the disorders in a more direct manner than prior treatments and therefore provides treatment with a greater degree of effectiveness.